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Stroke: Classification, Diagnosis, and Management

Overview

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Classification

1. Ischemic Stroke (~80%)

• Carotid/vertebral dissection (leading determined cause in the young - may follow minor trauma, sneezing, yoga, spinal manipulation)
• Antiphospholipid syndrome, protein C/S deficiency
• Oral contraceptives, pregnancy
• Sickle cell anemia, polycythemia
• Fibromuscular dysplasia
• Cocaine/amphetamine vasospasm
• Varicella or fungal vasculopathy

Transient Ischemic Attack (TIA)

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2. Hemorrhagic Stroke (~20%)

• Risk factors: hypertension (most common), older age, Black/Asian race, high alcohol use, low LDL/triglycerides
• Causes: hypertension, cerebral amyloid angiopathy (CAA in elderly), AVM, coagulopathy, anticoagulant use, tumor, cocaine
• CT appearance: round/oval hyperdense lesion (40-60 HU early, 80-100 HU over days)

• Bleeding between arachnoid and pia mater
• Classic: thunderclap headache ("worst headache of my life"), ruptured aneurysm
• CT may miss; LP shows xanthochromia if CT negative

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Stroke Mimics (Differential Diagnosis)

• Hypoglycemia (most important - can mimic stroke for days)
• Todd's paralysis (postictal focal weakness)
• Subdural/epidural hematoma
• Brain tumor or abscess
• Complex migraine with aura
• Wernicke encephalopathy (ophthalmoplegia + ataxia + confusion mimics cerebellar stroke)
• Bell's palsy, vestibular neuronitis, Ménière disease
• Giant cell arteritis

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Diagnosis

Immediate Evaluation (NINDS Target Times)

Neuroimaging

• Immediately distinguishes ischemic from hemorrhagic stroke
• Highly sensitive for parenchymal hemorrhage >1 cm and SAH
• Early ischemic changes (within 3 hours): hyperdense artery sign, sulcal effacement, loss of insular ribbon, gray-white interface loss, acute hypodensity (seen in up to 67% within 3 hours)
• Gross infarct signs typically not visible for 6-12 hours

• Run concurrently with CT head
• Identifies large vessel occlusion (LVO) for thrombectomy triage
• Also detects dissection, stenosis

• Identifies salvageable penumbra in extended time windows (6-24 hours)
• Generally not needed in first 6 hours

• Much higher sensitivity for ischemic stroke than CT, especially posterior fossa and within first hours
• DWI-FLAIR mismatch: DWI-positive + FLAIR-negative = stroke likely within ~4.5 hours (useful for "wake-up" strokes)
• Standard imaging for thrombectomy in 6-24 hour window (DAWN/DEFUSE-3 protocols)

Other Workup

• ECG - identify AF and acute MI
• Blood glucose - immediately (hypo/hyperglycemia mimics stroke)
• CBC, coagulation studies, BMP, troponin
• Echocardiography - cardioembolic source
• Carotid duplex / CTA neck - stenosis, dissection
• Cardiac monitoring (48-72h or longer) - paroxysmal AF detection

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Management

A. General Supportive Care (All Stroke Types)

• Airway/Breathing/Circulation - supplemental O2 only if SpO2 <94%
• IV access - avoid overhydration (cerebral edema risk); use isotonic saline; avoid dextrose solutions in normoglycemic patients
• Temperature - treat fever (>38°C) aggressively; even mild hyperthermia worsens neurologic injury
• Blood glucose - target 140-180 mg/dL; treat hypoglycemia (<60 mg/dL) with IV dextrose
• Swallowing assessment - NPO until evaluated (aspiration risk)
• Document exact time of last known well - determines eligibility for reperfusion

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B. Ischemic Stroke Management

Blood Pressure

• Without thrombolysis: withhold antihypertensives unless SBP >220 mmHg, DBP >120 mmHg, or MAP >130 mmHg (permissive hypertension preserves penumbral perfusion)
• Before thrombolysis: lower to <185/110 mmHg before starting tPA
• After thrombolysis: maintain <180/105 mmHg for 24 hours; monitor BP every 15 min during infusion, then every 30 min for 6h, then hourly for 16h

• Labetalol 10-20 mg IV over 1-2 min (may repeat once)
• Nicardipine infusion 5 mg/h, titrate by 2.5 mg/h every 5-15 min (max 15 mg/h)
• Clevidipine 1-2 mg/h IV, double dose every 2-5 min (max 21 mg/h)

Reperfusion Therapy

• Dose: 0.9 mg/kg IV (max 90 mg); 10% as bolus over 1 min, remainder over 60 min
• Time window: within 3 hours (FDA-approved); up to 4.5 hours for eligible patients
• Contraindications include: recent surgery, active bleeding, prior ICH, BP consistently >185/110 mmHg (untreated), INR >1.7, heparin use within 48h with elevated aPTT, glucose <50 or >400 mg/dL

• Single IV bolus, simpler administration; approved as alternative
• Dose: 0.25 mg/kg IV (max 25 mg)

• For large vessel occlusion (LVO) confirmed on CTA (ICA, M1/M2 MCA, basilar artery)
• Time window: 0-6 hours (standard); 6-24 hours in selected patients with favorable penumbra imaging (DAWN/DEFUSE-3 criteria: target mismatch on CTP or DWI/PWI-MRI)
• Maintain BP ≤185/110 mmHg pre-procedure (if no prior IV tPA)
• Give IV tPA first if eligible; do NOT delay tPA to wait for thrombectomy

Antiplatelet Therapy

• Aspirin 325 mg within 24-48 hours of ischemic stroke (not within 24h of tPA)
• For minor stroke / high-risk TIA: dual antiplatelet (aspirin + clopidogrel) for 21 days (POINT/CHANCE trial evidence)
• Anticoagulation for cardioembolic stroke (AF): start after 4-14 days depending on stroke size; DOAC preferred over warfarin

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C. Hemorrhagic Stroke Management

Intracerebral Hemorrhage (ICH)

• Reverse coagulopathy immediately: elevated INR - give vitamin K + 4-factor PCC (or FFP); dabigatran - idarucizumab; Xa inhibitors - andexanet alfa
• Blood pressure: if SBP 150-220 mmHg, acute lowering to target SBP 140 mmHg is safe and reasonable; reduces hematoma expansion
• Seizure prophylaxis: treat clinical seizures with antiepileptics; prophylactic treatment controversial
• Intracranial pressure management if elevated: HOB elevation 30°, hypertonic saline, osmotic therapy (mannitol), intubation/sedation, hemicraniectomy in refractory cases
• Glucose management: avoid hyper- and hypoglycemia
• Surgical evacuation: consider for cerebellar hemorrhage >3 cm, or accessible lobar clot with deterioration; deep basal ganglia hemorrhage generally not operated (no mortality benefit)

Subarachnoid Hemorrhage (SAH)

• Neurosurgical/neurovascular emergency
• Secure aneurysm (coiling or clipping) early
• Nimodipine 60 mg q4h for 21 days (reduces vasospasm-related deficit)
• Monitor for hydrocephalus (external ventricular drain)
• Triple-H therapy (hypertension, hypervolemia, hemodilution) for delayed cerebral ischemia (vasospasm)

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Stroke Risk Factors and Secondary Prevention

• Hypertension (strongest risk factor - present in most stroke patients; SBP ≥140 or DBP ≥90 mmHg)
• Atrial fibrillation (~5x risk)
• Diabetes mellitus
• Dyslipidemia
• Smoking
• Physical inactivity

• Antiplatelet therapy (aspirin, clopidogrel, or aspirin + dipyridamole)
• Anticoagulation for AF (DOAC preferred)
• Statin therapy (high-intensity)
• Carotid endarterectomy or stenting if symptomatic stenosis >50% (CEA preferred for >70%)
• BP control (target <130/80 mmHg)
• Lifestyle modification

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Prognosis

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Clinical Features of Stroke

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General Presenting Features

• Unilateral face/arm/leg weakness or numbness
• Speech difficulty (aphasia or dysarthria)
• Visual disturbance (monocular loss, hemianopia, diplopia)
• Severe headache (especially hemorrhagic stroke - "worst ever")
• Vertigo, ataxia, imbalance
• Altered consciousness or confusion

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Anterior Circulation Syndromes

Internal Carotid Artery (ICA)

• Ipsilateral amaurosis fugax - transient monocular blindness from emboli to the ophthalmic artery (this distinguishes ICA from pure MCA syndrome)
• Contralateral hemiplegia, hemisensory loss
• Homonymous hemianopia
• Aphasia if dominant hemisphere

Middle Cerebral Artery (MCA) - Most Common Stroke Territory

• Alexia with agraphia (angular gyrus)
• Gerstmann syndrome (left angular/parietal gyrus): finger agnosia + acalculia + right-left disorientation + agraphia
• Conduction aphasia, transcortical aphasia (depending on extent)
• Anosognosia (denial of hemiparesis, more common with right hemisphere lesions)

• Hemi-inattention, tactile and visual extinction
• Anosognosia, anosodiaphoria
• Apraxia, impaired prosody
• Acute agitated delirium (rarely)

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Anterior Cerebral Artery (ACA) - <3% of infarcts

• Contralateral leg > arm weakness (the leg is represented medially, which is ACA territory)
• Discriminative and proprioceptive sensory loss (lower extremity)
• Abulia (reduced motivation, flat affect)
• Akinetic mutism with bilateral mesiofrontal damage
• Transcortical motor aphasia (dominant hemisphere)
• Left arm apraxia (anterior corpus callosum disconnection)
• Sphincter incontinence
• Paratonia (gegenhalten)

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Anterior Choroidal Artery

1. Hemiparesis (posterior limb of internal capsule)
2. Hemisensory loss (posterolateral thalamus or thalamocortical fibers)
3. Hemianopia (lateral geniculate body or geniculo-calcarine tract) - with characteristic sparing of the horizontal meridian

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Lacunar Syndromes (Small-Vessel / Deep Perforator Occlusion)

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Posterior Circulation Syndromes

Posterior Cerebral Artery (PCA)

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Thalamic Infarction

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Cerebellar Syndromes

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Brainstem Syndromes

Midbrain

Pons

Medulla

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Watershed (Border Zone) Infarctions

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Hemorrhagic Stroke: Clinical Clues

• Sudden, severe headache at onset ("thunderclap")
• Rapid progression to coma or obtundation
• Vomiting at onset
• Very high blood pressure at presentation
• Stiff neck (suggests SAH)
• Onset during exertion

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NIHSS Assessment

• Mild: NIHSS 1-4
• Moderate: NIHSS 5-15
• Severe: NIHSS 16-20
• Very severe: NIHSS >20

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Stroke: Diagnosis and Investigations

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Step 1 - Immediate Bedside Evaluation (Before Imaging)

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Step 2 - Emergency Brain Imaging

A. Non-Contrast CT Head (NCCT) - FIRST-LINE

• Low sensitivity for posterior fossa ischemia (skull base streak artifacts)
• Cannot detect ischemia in first few hours
• Cannot identify penumbra or tissue viability

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B. CT Angiography (CTA) - Run Concurrently with CT Head

• Identifies large vessel occlusion (LVO) - M1/M2 MCA, ICA, basilar artery - triage for thrombectomy
• Detects vessel dissection (carotid or vertebral)
• Identifies stenosis, aneurysm (cause of SAH)
• Hyperdense dot sign on CTA correlates with proximal occlusion

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C. CT Perfusion (CTP)

• Extended time window (6-24 hours) - DAWN and DEFUSE-3 trial criteria
• Unknown onset "wake-up strokes"
• Not routinely needed in the first 6 hours

• CBF (cerebral blood flow) - reduced in ischemia
• CBV (cerebral blood volume) - core infarct has reduced CBV; penumbra may maintain CBV
• MTT/Tmax - prolonged in ischemic tissue
• Core vs. penumbra mismatch - core = irreversible damage; penumbra = salvageable tissue

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D. MRI Brain - Superior Sensitivity for Ischemia

• Posterior fossa / brainstem lesions
• Small lacunar infarcts
• Within the first few hours

DWI-ADC Correlation: Key to Lesion Age

DWI-FLAIR Mismatch (Wake-Up Stroke Rule)

• DWI positive + FLAIR negative = stroke onset likely within 4.5 hours - may be eligible for tPA even with unknown onset time
• DWI positive + FLAIR positive = stroke onset likely >4.5-6 hours ago - proceed to perfusion imaging

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CT vs MRI - Practical Choice

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Step 3 - Vascular Imaging

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Step 4 - Cardiac Investigations

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Step 5 - Laboratory Investigations

Immediate (all patients - results required before tPA)

Urgent (within hours)

Specialized / Etiologic (selected patients)

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Step 6 - Additional Investigations

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Summary: Diagnostic Algorithm

Acute neurological deficit
          ↓
Bedside glucose + NIHSS + ECG monitoring
          ↓
NCCT head (within 25 min of arrival)
     /              \
Hemorrhage        No hemorrhage
    ↓                   ↓
ICH/SAH             CTA head+neck (concurrent)
confirmed              ↓
    ↓           LVO identified?
Hemorrhagic       /         \
management       Yes          No
             Thrombectomy   tPA if eligible
             workup         (window + criteria)
                            ↓
                    MRI if unknown onset,
                    posterior fossa, or
                    6-24h window candidate
                    (DWI-FLAIR / DWI-PWI mismatch)
                            ↓
                 Etiologic workup:
              Echo + cardiac monitoring
              + vascular imaging +
              laboratory panel

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• Immediate actions on suspected stroke (all patients)
• Emergency CT to differentiate hemorrhagic from ischemic
• Hemorrhagic branch - ICH and SAH specific management
• Ischemic branch - tPA eligibility criteria and dosing, plus LVO/thrombectomy pathway
• General ischemic stroke care applicable to all patients at the bottom